These data support the working hypothesis that ICER functions as an antioncogene in mammalian cells, since its expression decelerates the uncontrollable cell growth which is characteristic of malignant cells. To test this hypothesis, the following specific aims are proposed: 1) to further characterize the role of ICERIIgamma in the AtT20 cell cycle, 2) to determine the role of ICERIIgamma in cell growth, proliferation and the process of oncogenesis, and 3) to determine whether ICERIIgamma activity is regulated by phosphorylation. These aims will be achieved by assessment of the effects of overexpression of ICERIIgamma in specific mammalian cell systems. Completion of these aims will allow a more comprehensive understanding of the role played by the cAMP pathway and the CREM gene in cell growth, differentiation and tumorigenesis. These results will therefore have a significant impact upon understanding of proliferation of normal and neoplastic cells.